ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.3545G>A (p.Arg1182Gln)

dbSNP: rs193922400
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029257 SCV000051903 likely pathogenic Neonatal diabetes mellitus 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Invitae RCV001388602 SCV001589658 pathogenic not provided 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1182 of the ABCC8 protein (p.Arg1182Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with neonatal diabetes mellitus (PMID: 16885549, 17446535, 22749773, 24622368). This variant is also known as Arg1183Gln. ClinVar contains an entry for this variant (Variation ID: 35611). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 22451668). For these reasons, this variant has been classified as Pathogenic.
PerkinElmer Genomics RCV001388602 SCV002023927 likely pathogenic not provided 2020-03-13 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000193953 SCV002070463 pathogenic Diabetes mellitus, transient neonatal, 2 2019-06-17 no assertion criteria provided clinical testing DNA sequence analysis of the ABCC8 gene demonstrated a sequence change, c.3545G>A, in exon 28 that results in an amino acid change, p.Arg1182Gln. This sequence change has been previously described in patients with transient neonatal diabetes, in both the de novo (PMID: 17389331) and familial state (PMIDs: 16885549, 22749773). It was identified in a father of one patient who presented with type 2 diabetes occurring later in life which was treated with diet alone (PMID: 16885549). Another missense variant affecting the same amino acid residue, p.Arg1182Trp, has also been described in patients with neonatal diabetes presenting with severe hyperglycemia (Flanagan et al., 2007). This sequence change has not been described in the population databases such as ExAC and gnomAD (dbSNP rs193922400). The p.Arg1182Gln change affects a highly conserved amino acid residue located in a functional domain of the ABCC8 protein that is known to be functional.

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